Title

A Study of AST-120 for Evaluating Prevention of Progression In Chronic Kidney Disease Including Assessment of Quality of Life (EPPIC-2)
A Phase III, Randomized, Double-Blind, Placebo-Controlled Study of AST-120 for Prevention of Chronic Kidney Disease Progression in Patients With Moderate to Severe Chronic Kidney Disease Including Assessment of Quality of Life
  • Phase

    Phase 3
  • Study Type

    Interventional
  • Intervention/Treatment

    kremezin ...
  • Study Participants

    1015
1) To evaluate the effectiveness of AST-120 (spherical carbon adsorbent) added to standard-of-care therapy in moderate to severe Chronic Kidney Disease (CKD), on time to first occurrence of any event of the triple composite outcome of initiation of dialysis, kidney transplant or doubling of serum creatinine (sCr) when compared with placebo; 2) To evaluate the safety and tolerability of long-term AST-120 therapy in patients with CKD; 3) To evaluate the effects of AST-120 versus placebo, on other measures of renal function and quality of life.
Study Started
Jul 31
2007
Primary Completion
Oct 31
2011
Study Completion
Oct 31
2011
Results Posted
Mar 02
2015
Estimate
Last Update
Jun 07
2022

Drug Placebo

9g /day (3 times a day)

Drug AST-120

9g /day (3 times a day)

Placebo Placebo Comparator

AST-120 Experimental

Criteria

Inclusion Criteria:

Age 18 years or older
Moderate to severe CKD, not anticipated to require dialysis or renal transplant within the next 6 months
Patient survival expected to be no less than one year
Serum creatinine in men >= 2.0 mg/dL (>= 177 µmol/L) and <= 5.0 mg/dL (<= 442 µmol/L), and in women >= 1.5 mg/dL (>= 133 µmol/L) and <= 5.0 mg/dL (<= 442 µmol/L) at Screening
Urinary total protein to urinary total creatinine ratio must be >= 0.5 on a spot void obtained at Screening
Blood pressure <= 160/90 mmHg at both Screening and Baseline visits. In addition, blood pressure, if measured, must have been stable in hypertensive patients over the 3 months prior to Screening, with no more than 1 blood pressure reading > 160/90 mmHg
In patients being treated for hypertension, they should be on a stable anti-hypertensive regimen

Exclusion Criteria:

Obstructive or reversible cause of kidney disease
Nephrotic syndrome defined as a ratio of urinary total protein to urinary creatinine of > 6.0 as measured on a spot void
Adult polycystic kidney disease
History of previous kidney transplant
History of recent (within the past 6 months) accelerated or malignant hypertension
Uncontrolled arrhythmia or severe cardiac disease within the past 6 months
History of malabsorption, inflammatory bowel disease, hiatal hernia, active peptic ulcer, or severe GI dysmotility, not attributable to the use of a phosphate binder
Received any investigational agent or participated in a clinical study within the previous 3 months
Presence of any significant medical condition that might create an undue risk with study participation, or significantly confound the collection of safety and efficacy data in this study

Summary

AST-120

Placebo

All Events

Event Type Organ System Event Term AST-120 Placebo

Composite of Dialysis Initiation, Kidney Transplantation, and Serum Creatinine Doubling. Number of Participants Meeting the Criteria Are Reported.

AST-120

172.0
participants

Placebo

183.0
participants

Number of Participants With Treatment-emergent Adverse Events and Treatment-emergent Serious Adverse Events

AST-120

Treatment-emergent AE

Treatment-emergent SAE

Placebo

Treatment-emergent AE

Treatment-emergent SAE

Vitamin A Levels

AST-120

Baseline

1143.6
ng/mL (Mean)
Standard Deviation: 398.42

Early Term/ Discontinuation

1231.2
ng/mL (Mean)
Standard Deviation: 442.79

Final Visit

1223.3
ng/mL (Mean)
Standard Deviation: 393.07

Week 108

1231.2
ng/mL (Mean)
Standard Deviation: 397.68

Week 12

1098.9
ng/mL (Mean)
Standard Deviation: 376.33

Week 120

1240.8
ng/mL (Mean)
Standard Deviation: 387.79

Week 132

1253.2
ng/mL (Mean)
Standard Deviation: 376.03

Week 144

1324.6
ng/mL (Mean)
Standard Deviation: 567.01

Week 156

1196.3
ng/mL (Mean)
Standard Deviation: 456.16

Week 168

1265.0
ng/mL (Mean)
Standard Deviation: 478.26

Week 180

1243.4
ng/mL (Mean)
Standard Deviation: 454.73

Week 24

1106.0
ng/mL (Mean)
Standard Deviation: 371.04

Week 36

1118.4
ng/mL (Mean)
Standard Deviation: 382.22

Week 48

1117.0
ng/mL (Mean)
Standard Deviation: 380.72

Week 60

1162.6
ng/mL (Mean)
Standard Deviation: 373.49

Week 72

1157.6
ng/mL (Mean)
Standard Deviation: 397.82

Week 84

1225.6
ng/mL (Mean)
Standard Deviation: 418.23

Week 96

1219.5
ng/mL (Mean)
Standard Deviation: 419.49

Placebo

Baseline

1159.4
ng/mL (Mean)
Standard Deviation: 404.85

Early Term/ Discontinuation

1269.4
ng/mL (Mean)
Standard Deviation: 425.09

Final Visit

1274.5
ng/mL (Mean)
Standard Deviation: 350.67

Week 108

1266.6
ng/mL (Mean)
Standard Deviation: 427.25

Week 12

1182.9
ng/mL (Mean)
Standard Deviation: 411.38

Week 120

1198.7
ng/mL (Mean)
Standard Deviation: 388.77

Week 132

1234.2
ng/mL (Mean)
Standard Deviation: 365.55

Week 144

1204.5
ng/mL (Mean)
Standard Deviation: 414.34

Week 156

1193.0
ng/mL (Mean)
Standard Deviation: 389.27

Week 168

1363.7
ng/mL (Mean)
Standard Deviation: 348.93

Week 180

1147.8
ng/mL (Mean)
Standard Deviation: 254.30

Week 24

1180.5
ng/mL (Mean)
Standard Deviation: 385.83

Week 36

1201.6
ng/mL (Mean)
Standard Deviation: 401.03

Week 48

1196.7
ng/mL (Mean)
Standard Deviation: 399.97

Week 60

1242.3
ng/mL (Mean)
Standard Deviation: 421.19

Week 72

1243.5
ng/mL (Mean)
Standard Deviation: 416.84

Week 84

1249.3
ng/mL (Mean)
Standard Deviation: 379.41

Week 96

1267.8
ng/mL (Mean)
Standard Deviation: 376.38

Vitamin B12 Levels

AST-120

Baseline

651.7
pg/mL (Mean)
Standard Deviation: 1961.13

Early Term/ Discontinuation

1186.2
pg/mL (Mean)
Standard Deviation: 4148.50

Final Visit

764.2
pg/mL (Mean)
Standard Deviation: 2392.88

Week 108

700.2
pg/mL (Mean)
Standard Deviation: 2110.74

Week 12

497.6
pg/mL (Mean)
Standard Deviation: 1466.88

Week 120

509.9
pg/mL (Mean)
Standard Deviation: 726.72

Week 132

657.7
pg/mL (Mean)
Standard Deviation: 1428.09

Week 144

416.3
pg/mL (Mean)
Standard Deviation: 211.52

Week 156

601.5
pg/mL (Mean)
Standard Deviation: 744.06

Week 168

552.7
pg/mL (Mean)
Standard Deviation: 570.85

Week 180

494.5
pg/mL (Mean)
Standard Deviation: 389.57

Week 24

608.4
pg/mL (Mean)
Standard Deviation: 2016.76

Week 36

631.8
pg/mL (Mean)
Standard Deviation: 2079.77

Week 48

455.2
pg/mL (Mean)
Standard Deviation: 371.17

Week 60

444.4
pg/mL (Mean)
Standard Deviation: 332.65

Week 72

601.6
pg/mL (Mean)
Standard Deviation: 1882.39

Week 84

465.2
pg/mL (Mean)
Standard Deviation: 637.01

Week 96

444.8
pg/mL (Mean)
Standard Deviation: 364.90

Placebo

Baseline

747.9
pg/mL (Mean)
Standard Deviation: 2521.02

Early Term/ Discontinuation

1174.8
pg/mL (Mean)
Standard Deviation: 3403.80

Final Visit

505.5
pg/mL (Mean)
Standard Deviation: 1063.91

Week 108

505.6
pg/mL (Mean)
Standard Deviation: 771.70

Week 12

464.3
pg/mL (Mean)
Standard Deviation: 650.01

Week 120

689.1
pg/mL (Mean)
Standard Deviation: 1864.40

Week 132

476.9
pg/mL (Mean)
Standard Deviation: 483.88

Week 144

721.3
pg/mL (Mean)
Standard Deviation: 1543.37

Week 156

1046.6
pg/mL (Mean)
Standard Deviation: 3595.42

Week 168

750.2
pg/mL (Mean)
Standard Deviation: 1385.54

Week 180

1062.7
pg/mL (Mean)
Standard Deviation: 2386.40

Week 24

681.0
pg/mL (Mean)
Standard Deviation: 2127.01

Week 36

618.7
pg/mL (Mean)
Standard Deviation: 2031.35

Week 48

728.4
pg/mL (Mean)
Standard Deviation: 2412.07

Week 60

637.8
pg/mL (Mean)
Standard Deviation: 1911.72

Week 72

741.3
pg/mL (Mean)
Standard Deviation: 2281.81

Week 84

740.9
pg/mL (Mean)
Standard Deviation: 2492.87

Week 96

459.5
pg/mL (Mean)
Standard Deviation: 548.84

25-Hydroxyvitamin D Levels

AST-120

Baseline

21.09
ng/mL (Mean)
Standard Deviation: 10.391

Early Term/ Discontinuation

22.18
ng/mL (Mean)
Standard Deviation: 13.112

Final Visit

24.62
ng/mL (Mean)
Standard Deviation: 11.311

Week 108

22.97
ng/mL (Mean)
Standard Deviation: 10.305

Week 12

21.64
ng/mL (Mean)
Standard Deviation: 9.981

Week 120

24.45
ng/mL (Mean)
Standard Deviation: 11.315

Week 132

25.5
ng/mL (Mean)
Standard Deviation: 11.083

Week 144

25.02
ng/mL (Mean)
Standard Deviation: 10.830

Week 156

27.3
ng/mL (Mean)
Standard Deviation: 14.396

Week 168

28.87
ng/mL (Mean)
Standard Deviation: 12.654

Week 180

33.63
ng/mL (Mean)
Standard Deviation: 15.515

Week 24

21.7
ng/mL (Mean)
Standard Deviation: 10.166

Week 36

21.72
ng/mL (Mean)
Standard Deviation: 10.441

Week 48

21.1
ng/mL (Mean)
Standard Deviation: 10.195

Week 60

21.39
ng/mL (Mean)
Standard Deviation: 10.139

Week 72

22.56
ng/mL (Mean)
Standard Deviation: 11.326

Week 84

22.29
ng/mL (Mean)
Standard Deviation: 9.967

Week 96

22.63
ng/mL (Mean)
Standard Deviation: 10.563

Placebo

Baseline

20.36
ng/mL (Mean)
Standard Deviation: 10.063

Early Term/ Discontinuation

21.32
ng/mL (Mean)
Standard Deviation: 10.752

Final Visit

24.03
ng/mL (Mean)
Standard Deviation: 11.099

Week 108

22.17
ng/mL (Mean)
Standard Deviation: 11.535

Week 12

21.08
ng/mL (Mean)
Standard Deviation: 10.246

Week 120

22.55
ng/mL (Mean)
Standard Deviation: 12.332

Week 132

22.33
ng/mL (Mean)
Standard Deviation: 11.377

Week 144

21.06
ng/mL (Mean)
Standard Deviation: 9.960

Week 156

21.46
ng/mL (Mean)
Standard Deviation: 10.506

Week 168

23.91
ng/mL (Mean)
Standard Deviation: 11.704

Week 180

25.72
ng/mL (Mean)
Standard Deviation: 8.827

Week 24

21.28
ng/mL (Mean)
Standard Deviation: 10.100

Week 36

21.0
ng/mL (Mean)
Standard Deviation: 9.766

Week 48

20.57
ng/mL (Mean)
Standard Deviation: 10.489

Week 60

20.36
ng/mL (Mean)
Standard Deviation: 10.250

Week 72

21.58
ng/mL (Mean)
Standard Deviation: 11.225

Week 84

22.3
ng/mL (Mean)
Standard Deviation: 10.728

Week 96

21.83
ng/mL (Mean)
Standard Deviation: 10.463

Vitamin E Levels

AST-120

Baseline

16.55
ug/mL (Mean)
Standard Deviation: 6.204

Early Term/ Discontinuation

16.32
ug/mL (Mean)
Standard Deviation: 5.047

Final Visit

15.6
ug/mL (Mean)
Standard Deviation: 5.731

Week 108

17.27
ug/mL (Mean)
Standard Deviation: 6.403

Week 12

16.59
ug/mL (Mean)
Standard Deviation: 6.152

Week 120

16.95
ug/mL (Mean)
Standard Deviation: 5.217

Week 132

16.81
ug/mL (Mean)
Standard Deviation: 5.533

Week 144

17.11
ug/mL (Mean)
Standard Deviation: 6.970

Week 156

16.64
ug/mL (Mean)
Standard Deviation: 6.016

Week 168

16.64
ug/mL (Mean)
Standard Deviation: 6.435

Week 180

15.57
ug/mL (Mean)
Standard Deviation: 4.474

Week 24

16.87
ug/mL (Mean)
Standard Deviation: 6.146

Week 36

17.32
ug/mL (Mean)
Standard Deviation: 7.280

Week 48

17.12
ug/mL (Mean)
Standard Deviation: 6.653

Week 60

16.6
ug/mL (Mean)
Standard Deviation: 5.787

Week 72

16.79
ug/mL (Mean)
Standard Deviation: 6.188

Week 84

17.13
ug/mL (Mean)
Standard Deviation: 6.978

Week 96

17.42
ug/mL (Mean)
Standard Deviation: 6.987

Placebo

Baseline

16.29
ug/mL (Mean)
Standard Deviation: 6.188

Early Term/ Discontinuation

16.25
ug/mL (Mean)
Standard Deviation: 6.334

Final Visit

15.92
ug/mL (Mean)
Standard Deviation: 6.211

Week 108

17.03
ug/mL (Mean)
Standard Deviation: 5.986

Week 12

16.94
ug/mL (Mean)
Standard Deviation: 6.756

Week 120

16.79
ug/mL (Mean)
Standard Deviation: 5.870

Week 132

16.42
ug/mL (Mean)
Standard Deviation: 6.081

Week 144

17.06
ug/mL (Mean)
Standard Deviation: 6.607

Week 156

16.7
ug/mL (Mean)
Standard Deviation: 6.491

Week 168

18.02
ug/mL (Mean)
Standard Deviation: 6.865

Week 180

17.58
ug/mL (Mean)
Standard Deviation: 5.239

Week 24

16.82
ug/mL (Mean)
Standard Deviation: 6.275

Week 36

16.82
ug/mL (Mean)
Standard Deviation: 6.046

Week 48

16.95
ug/mL (Mean)
Standard Deviation: 6.204

Week 60

17.14
ug/mL (Mean)
Standard Deviation: 6.267

Week 72

17.1
ug/mL (Mean)
Standard Deviation: 6.242

Week 84

16.82
ug/mL (Mean)
Standard Deviation: 5.847

Week 96

17.21
ug/mL (Mean)
Standard Deviation: 6.007

Vitamin K Levels

AST-120

Baseline

0.663
ng/mL (Mean)
Standard Deviation: 0.6138

Early Term / Discontinuation

0.761
ng/mL (Mean)
Standard Deviation: 0.6920

Final Visit

0.843
ng/mL (Mean)
Standard Deviation: 0.7197

Week 108

0.801
ng/mL (Mean)
Standard Deviation: 0.7190

Week 12

0.651
ng/mL (Mean)
Standard Deviation: 0.6296

Week 120

0.688
ng/mL (Mean)
Standard Deviation: 0.7177

Week 132

0.782
ng/mL (Mean)
Standard Deviation: 0.7253

Week 144

0.661
ng/mL (Mean)
Standard Deviation: 0.6658

Week 156

0.685
ng/mL (Mean)
Standard Deviation: 0.6300

Week 168

0.822
ng/mL (Mean)
Standard Deviation: 0.7662

Week 180

0.879
ng/mL (Mean)
Standard Deviation: 0.8268

Week 24

0.655
ng/mL (Mean)
Standard Deviation: 0.5999

Week 36

0.73
ng/mL (Mean)
Standard Deviation: 0.6616

Week 48

0.626
ng/mL (Mean)
Standard Deviation: 0.5746

Week 60

0.695
ng/mL (Mean)
Standard Deviation: 0.6458

Week 72

0.703
ng/mL (Mean)
Standard Deviation: 0.6295

Week 84

0.775
ng/mL (Mean)
Standard Deviation: 0.7309

Week 96

0.723
ng/mL (Mean)
Standard Deviation: 0.6386

Placebo

Baseline

0.628
ng/mL (Mean)
Standard Deviation: 0.6023

Early Term / Discontinuation

0.679
ng/mL (Mean)
Standard Deviation: 0.6541

Final Visit

0.814
ng/mL (Mean)
Standard Deviation: 0.6982

Week 108

0.737
ng/mL (Mean)
Standard Deviation: 0.7428

Week 12

0.653
ng/mL (Mean)
Standard Deviation: 0.6060

Week 120

0.717
ng/mL (Mean)
Standard Deviation: 0.6918

Week 132

0.65
ng/mL (Mean)
Standard Deviation: 0.6832

Week 144

0.662
ng/mL (Mean)
Standard Deviation: 0.5824

Week 156

0.724
ng/mL (Mean)
Standard Deviation: 0.6570

Week 168

0.862
ng/mL (Mean)
Standard Deviation: 0.7611

Week 180

1.02
ng/mL (Mean)
Standard Deviation: 1.0008

Week 24

0.658
ng/mL (Mean)
Standard Deviation: 0.6364

Week 36

0.64
ng/mL (Mean)
Standard Deviation: 0.6120

Week 48

0.649
ng/mL (Mean)
Standard Deviation: 0.6211

Week 60

0.732
ng/mL (Mean)
Standard Deviation: 0.6640

Week 72

0.703
ng/mL (Mean)
Standard Deviation: 0.6668

Week 84

0.717
ng/mL (Mean)
Standard Deviation: 0.6631

Week 96

0.682
ng/mL (Mean)
Standard Deviation: 0.6382

Serum Folate Levels

AST-120

Baseline

15.51
ng/mL (Mean)
Standard Deviation: 28.300

Early Term/ Discontinuation

12.28
ng/mL (Mean)
Standard Deviation: 18.101

Final Visit

13.62
ng/mL (Mean)
Standard Deviation: 24.370

Week 108

12.76
ng/mL (Mean)
Standard Deviation: 18.758

Week 12

13.46
ng/mL (Mean)
Standard Deviation: 23.247

Week 120

12.34
ng/mL (Mean)
Standard Deviation: 13.152

Week 132

12.13
ng/mL (Mean)
Standard Deviation: 12.813

Week 144

14.26
ng/mL (Mean)
Standard Deviation: 31.355

Week 156

12.12
ng/mL (Mean)
Standard Deviation: 12.259

Week 168

13.9
ng/mL (Mean)
Standard Deviation: 16.225

Week 180

16.63
ng/mL (Mean)
Standard Deviation: 17.402

Week 24

13.79
ng/mL (Mean)
Standard Deviation: 28.539

Week 36

13.35
ng/mL (Mean)
Standard Deviation: 24.059

Week 48

13.84
ng/mL (Mean)
Standard Deviation: 24.193

Week 60

13.25
ng/mL (Mean)
Standard Deviation: 20.655

Week 72

12.78
ng/mL (Mean)
Standard Deviation: 21.370

Week 84

12.67
ng/mL (Mean)
Standard Deviation: 19.767

Week 96

13.27
ng/mL (Mean)
Standard Deviation: 18.484

Placebo

Baseline

18.87
ng/mL (Mean)
Standard Deviation: 37.577

Early Term/ Discontinuation

23.21
ng/mL (Mean)
Standard Deviation: 35.035

Final Visit

18.36
ng/mL (Mean)
Standard Deviation: 42.611

Week 108

17.1
ng/mL (Mean)
Standard Deviation: 42.133

Week 12

18.57
ng/mL (Mean)
Standard Deviation: 38.500

Week 120

18.93
ng/mL (Mean)
Standard Deviation: 46.884

Week 132

14.08
ng/mL (Mean)
Standard Deviation: 36.549

Week 144

9.93
ng/mL (Mean)
Standard Deviation: 9.423

Week 156

10.04
ng/mL (Mean)
Standard Deviation: 10.910

Week 168

17.62
ng/mL (Mean)
Standard Deviation: 31.941

Week 180

13.45
ng/mL (Mean)
Standard Deviation: 14.884

Week 24

17.44
ng/mL (Mean)
Standard Deviation: 39.950

Week 36

16.61
ng/mL (Mean)
Standard Deviation: 34.428

Week 48

18.16
ng/mL (Mean)
Standard Deviation: 40.329

Week 60

17.57
ng/mL (Mean)
Standard Deviation: 40.427

Week 72

17.76
ng/mL (Mean)
Standard Deviation: 38.679

Week 84

14.34
ng/mL (Mean)
Standard Deviation: 26.514

Week 96

17.2
ng/mL (Mean)
Standard Deviation: 37.621

Number of Participants Who Developed a Component of a Quadruple Composite Endpoint (Initiation of Dialysis, Kidney Transplant, Doubling of sCr, or Death)

AST-120

Placebo

Total

1015
Participants

Age, Continuous

55.1
years (Mean)
Standard Deviation: 15.11

Sex: Female, Male

Overall Study

AST-120

Placebo

Drop/Withdrawal Reasons

AST-120

Placebo